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Pain management and injury repair represent areas of significant clinical unmet need in Orthopedics and Sports medicine, especially in the management of chronic and degenerative connective tissue diseases such as osteoarthritis and tendinopathies. Trends in the clinical data from recent studies show autologous platelet-rich plasma (PRP) therapy is emerging as a safe and effective means for improving patient outcomes. However, the precise mechanisms through which PRP exerts its effects remain elusive, and there exists much controversy in the literature over what might comprise an “optimal” PRP formulation. Part of the controversy surrounding PRP formulation is there are many commercially available devices for PRP preparation that generate vastly different products that are not equivalent in cellular or biochemical composition. The range of different PRP products has led to the need for classification systems to indicate whether a given PRP contains high or low platelet concentrations, what the relative leukocyte content is, and whether it contains red blood cells (RBCs) as examples. Although autologous PRP has proven safe and effective in improving patient outcomes in a broad range of clinical applications regardless of formulation, a current area of active debate relates to the role of non-platelet cells in the mechanism of action of PRP, and in particular to what extent leukocytes and RBCs may enhance or detract from the presumed benefits of platelet action. Although very little is actually known about the roles of non-platelet blood components in the activity of platelets with respect to PRP therapy, there is a substantial body of literature relating to the roles of blood components in the physiology of normal wound repair. In a normal wound repair reaction all of the components of blood have important roles in driving the healing cascade, and the co-operative physiological balance of cellular and biochemical action results in restoration of the injured tissue to a healthy state. This narrative review article discusses the salient roles of each of the major blood components in normal wound repair and how these foundational principles may also relate to the mechanisms of PRP action.

Physiology of Blood Components in Wound Healing: an Appreciation of Cellular Co-Operativity in Platelet Rich Plasma Action